SCALE-UP STUDY ? ABSTRACT Depression causes a heavy burden of death and disability in low- and middle-income countries (LMICs), resulting in high societal, economic, and quality-of-life costs. Depression often co-occurs with chronic medical conditions whose prevalence is dramatically increasing in LMIC, such as hypertension and diabetes, and is associated with worse clinical outcomes for those comorbid conditions. This confluence has led to calls for integration of mental health treatment with expanding chronic disease care systems in LMICs. Response to the urgent need for mental health care is hampered by the severe shortage of skilled mental health professionals in LMICs. As a result, much attention in the global mental health community has focused on task-sharing approaches that give non-specialists, such as primary care providers or community workers, the skills and structure to address common mental health problems. The Malawi Ministry of Health has identified antidepressant treatment expansion in chronic diseases clinics as a high priority. Algorithm-based care for depression (ABCD) is a resource-efficient, evidence-based, task- sharing approach to antidepressant provision in non-psychiatric clinical settings involving systematic measures and algorithm-guided antidepressant treatment decisions designed for non-specialists. The availability and efficacy of low-cost antidepressants in many low-resource settings makes an approach like ABCD a highly promising strategy for efficient integration of depression treatment into existing clinical care systems. A key knowledge gap impeding the scale-up of ABCD in low-resource settings is the level of resource investment required to achieve acceptable fidelity and effectiveness in real-world clinics. Implementation science research to identify optimal implementation strategies will be critical to advance scale-up efforts. The overall objective of the Scale-Up Study Core is to identify the most efficient and effective design for the integration of ABCD into existing chronic disease care in Malawi and similar settings. The Scale-Up Study Core will conduct a clinic-randomized trial to compare the implementation, effectiveness, and cost- effectiveness outcomes of two implementation strategies to facilitate ABCD scale-up. The scale-up study will also generate information on whether clinics with certain characteristics will require additional resources in order to achieve sufficient ABCD fidelity. In coordination with the Capacity-Building Core, the scale-up study will provide invaluable ?on the job? training opportunities for select SHARP trainees to contribute to the design and conduct of a mental health-related implementation science research study. Finally, the results of the study will guide the drafting of a detailed revision to the national Mental Health Action Plan, in collaboration with the Ministry of Health and other SHARP partners. Overall, the activities of the Scale-Up Study Core will provide key information to guide the Malawi Ministry of Health in furthering its intention of scaling up evidence-based, resource-efficient depression treatment in existing chronic disease care settings.